Recombinant DNA Advisory Committee - 2/10-11/92 
while allowing the physician some recourse if there seems to be some problem associated 
with the treatment. 
Review— Mr. Barton 
Mr. Barton had two concerns about the protocol: (1) the development of lymphocytes in 
the presence of HIV virus, and (2) if the in vitro would be affected because of the presence 
of HIV antibody-producing components. The consent form has been satisfactorily revised 
to clarify that the inserted genes were providing a combination of marker function and the 
suicide gene function. 
Other comments 
Dr. Krogstad asked Dr. Greenberg to address the transition from the in vitro studies to the 
in vivo situation, and the likelihood that the ganciclovir strategy might not succeed because 
of the increased complexity of the in vivo situation. 
Dr. Post asked how long the procedure is for cloning and transduction, and he expressed 
concern about the risks of waiting for a BMT. There is evidence that two foreign proteins 
are likely to be immunogenic and that adding this gene may actually decrease the benefit 
from receiving transduced CD8 cells. 
Presentation— Dr. Greenberg 
Dr. Greenberg said that there is no reason to believe it will not be possible to reconstitute 
virus-specific immunity to HIV. Several reasons dictate the importance of using T-cell 
clones, including the ability to reconstitute immunity and to evaluate the effects of the 
procedure. The goal of the study is to reconstitute HIV-specific immunity in patients 
undergoing BMT. The nature of the problem is that there is now a large population of 
HIV-seropositive patients who are living much longer than their initial diagnosis. 
Subsequently, B-cell lymphomas are being identified more frequently in these patients 
since they are living longer. According to a recent study in the Journal of the National 
Cancer Institute , there will be about 10,000 cases of non-Hodgkin's lymphoma in 1992, 25% 
of which will be HIV-related. 
Based on this data, allogeneic BMT is being proposed as a potential therapy for patients 
who are HIV seropositive (but otherwise healthy) and have an histocompatibility antigen 
(HLA)-matched sibling as a potential bone marrow donor. The rationale for this proposal 
is that the lymphoma that occurs in these patients has been shown to be resistant to 
standard chemotherapy. Data in this area suggests that BMT with high-dose chemotherapy 
in combination with radiation therapy provides only a 40% chance of curing patients with 
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Recombinant DNA Research, Volume 15 
